|
Strategies for the Prevention
of Hepatitis B, Hepatitis C and Human Immunodeficiency
Virus infection in the Paediatric Population
of Developing Countries
Sina Aziz
(1)
Waris Qidwai (2)
(1) Sina Aziz, MBBS, DCPS (HPE), PhD.
Professor of Pediatrics, Department of Pediatrics,
Abbasi Shaheed Hospital,
Karachi Medical and Dental College, Block M,
North Nazimabad, Karachi,
Pakistan
(2) Waris Qidwai, MBBS, MCPS (FM), FCPS (FM),
FRCGP (INT), FCGP(SL), MFPH(UK)
Professor and Chairman, Department of Family
Medicine
Aga Khan University Hospital, Karachi,
Pakistan
Correspondence:
Dr. Waris Qidwai
The Tajuddin Chatoor
Professor and Chairman
Department of Family Medicine
Aga Khan University, Karachi
Stadium Road, PO Box: 3500
Karachi-74800, Pakistan
Tel: 92-21-3486-4842 (Office) 92-3332317836
(Cell)
Fax: 92-21-3493-4294
Email: waris.qidwai@aku.edu
|
Abstract
After
a brief background about the epidemiology
of Hepatitis B, C and HIV, strategies
for their prevention are discussed in
the paediatric population of developing
countries. These strategies are focused
on mother to child transmission, misuse
of injections, use of infected needles,
myths and use of material infected with
the hepatitis positive patient such as
a comb, tooth brush etc. Malnutrition
and its relationship with Tuberculosis
and HIV infection are discussed. World
Health Organization (WHO) guidelines on
the management of malnutrition, Tuberculosis
and HIV are discussed briefly. A real
scenario highlighting the existence of
HBV, HCV and HIV is described. Finally
role of policy makers, NGO, WHO and local
governments in the prevention of HBV,
HCV and HIV in the paediatric population
is discussed.
Key words:
Hepatitis B; Hepatitis C; Human Immunodeficiency
Virus infection; Paediatric population
|
At global level, HBV, HCV and HIV infected
population stands at 370, 130 and 40 million
respectively. HIV and HBV co-infection are 2-4
million, while HIV and HCV co-infection are
4-5 million(1). Transmission of these infections
varies and is dependent upon the geographic
region and local practices e.g. in some areas
of the world where men who have sex with men,
these infections are more common. Hepatitis
infections HBV and HCV are endemic in some of
the developing countries(1).
Among persons with HBV, HCV and HIV co infections,
the presenting features are different. They
are dependent upon the epidemiology of the infection
in a particular geographical region. As the
epidemiology of an infection changes over time,
surveys are needed which will detect these epidemiological
changes over time and hence can help in developing
strategies to prevent these infections in a
particular region or communities(2).
HBV is caused by a DNA virus, while HCV by
a RNA virus. These viruses cause acute and chronic
liver disease worldwide, leading to cirrhosis
and hepatocellular carcinoma (HCC). There is
difference in the clinical presentation, pathology
and outcome in patients with HCC depending upon
whether the cause is HBV or HCV. This difference
affects the cure rate and the prognosis(3).
HBV and HCV are blood borne viruses; however,
HBV can be transmitted by both percutaneous
and mucosal exposures and HCV by percutaneous
exposure(4). Transmission of these viruses most
commonly occurs in developing countries by misuse
of infected syringes and rarely by vertical
transmission(5, 6) child abuse and possible
risk of co-existence of HBV, HCV and HIV infection
in garbage scavengers from poor communities(7)
(Figure 1) tattooing in older children, drug
abuse, and needle piercing(8, 9).
HBV prevention is achieved by immunization for
all children according to the Expanded Program
for Immunization (EPI) (10, 11). Some centers
are giving a booster dose of hepatitis B vaccine,
11-15 years after the primary vaccination. A
study done in China indicates that in those
children with a low level (0.1-0.9 and <0.1mlU/mL)
of the anti-HBs titer, prior to the booster
vaccine may need more than one booster dose
vaccination. While in those children with a
higher level of pre-booster anti-HBs titer of
1-9.9mlU/mL, additional booster vaccination
dose is not required. Hence, the protective
levels of the HBs antibody decrease more rapidly
in those with low titers(11, 12).
The vaccine for HCV is not available, even though
trials on the vaccine development are being
conducted(12). Lack of availability of the vaccine
against HCV is a serious concern as there will
be an upsurge of HCV infections compared to
HBV infection, leading to more cases of HCC.
Adolescent children are more prone to infections
related to drug abuse and sexual intercourse(13).
HIV infection numbers in Southeast Asia was
320,000 in the year 2001, but has now declined
to 210,000 in the year 2010. The countries of
the WHO Southeast Asia Region (SEAR) (14) include
Bangladesh, Bhutan, South Korea, India, Indonesia,
the Maldives, Myanmar, Nepal, Sri Lanka, Thailand,
and Timor-Leste. The largest numbers of cases
are from Indonesia, where the number of HIV
infections is increasing. In the remaining countries
of SEAR region, the number of HIV positive cases
is decreasing. The maximum number of cases reported
from SEARS after Indonesia is from India, which
has the second highest number of cases in the
region due to heterosexual intercourse(14).
Some older children practice anal intercourse
that may also result in HIV infections(15).
HIV positive men are more likely to have sexual
abuse with children than HIV negative men(16).
Knowledge of the children is inadequate regarding
HIV infection transmission and they represent
the vulnerable group(17).
Prevention strategies for HIV infection in children
are the same as for hepatitis viruses and focus
on mother-to-child transmission of HIV from
an HIV-infected woman to her child during pregnancy,
childbirth (also called labor and delivery),
or breastfeeding. Mother-to-child transmission
is the most common way that children become
infected with HIV(18).
Pregnant women infected with HIV are given medications
for the HIV infection during pregnancy and at
childbirth. Elective Cesarean section may be
done to prevent HIV infection from mother to
child. A baby born to a mother with HIV infection
will receive HIV medication for 6 weeks after
birth. The medications will reduce the risk
of HIV infection transmitted from the mother
to the newborn baby(18).
HIV can be transmitted via breast milk. Hence
women in the USA are advised not to breast feed
their babies if they are suffering from HIV
infection. In such cases formula milk is a safe
and healthy alternative to breast milk(19).
However, breast-feeding is promoted in developing
countries regardless of HBV, HCV or HIV infection
in mother. In developing countries, due to risk
of malnutrition in children, the morbidity and
mortality is high. Approximately half of the
deaths, which occur in children under five years
of age, are due to malnutrition. This results
in loss of 3 million deaths every year, which
could have been prevented. Recurrent infections
in children with malnutrition leads to a vicious
cycle with delayed recovery and makes the child
more prone to susceptible infections leading
to death(20). In babies, who are not breast
fed, milk is given to them in contaminated bottles
and water used is not consumable for health,
hence it is advised to continue breast-feeding
in these areas. Thus in countries with poor
socio-economic backgrounds, with mothers infected
with HBV or HCV or HIV, exclusive breastfeeding
is recommended. Breast feeding in HIV-infected
mothers is continued for the first six months
of life, unless replacement feeding is acceptable,
feasible, affordable, sustainable and safe for
their infants(19, 20).
In areas with poor social and health sector
development, incidence of HCV and HIV is high.
Drug addicts have to cope not only with their
addiction but also with the process of social
exclusion. To the greatest extent possible,
any course of action for such a group should
be built into integrated, coordinated plans
that take a broad approach to the main issues
involved(21).
|
CO-INFECTION OF TUBERCULOSIS (TB) AND HIV |
Both children and adults may be co-infected
with HIV and tuberculosis. In children, data
available on TB and HIV co-infection is rare.
However, a strong suspicion of HIV must be kept
in mind for HIV when TB is diagnosed in any
child, especially if HIV is endemic in that
particular region or the child is immunocompromised.
Hence the awareness among paediatricians when
managing children with severe malnutrition and
in case of history of contact with a TB patient,
the child must be investigated for HIV also
after appropriate counseling of the parents.
This may occur in Multi drug resistant cases
of tuberculosis (MDR TB) and co-existing HIV
infections. WHO has suggested a special team,
which can manage these patients (22). Since
HIV infection can occur in immuno-compromised
children, with tuberculosis, prevention of tuberculosis
in developing countries should focus on curtailing
the epidemic of TB and HIV especially in endemic
areas. Strict control of the vaccination program,
protection of children from exposure to infected
individuals with TB and prevention of patient
transfer with active transfer from one country
to another should be monitored(23).
Diagnosis of HIV/TB co-infection in children
is challenging. Paediatric TB and HIV(22,23)
have overlapping clinical manifestations, which
could lead to missed or late diagnosis.
| HBV,
HCV
AND
HEPATITIS
D
(HDV)
CO-INFECTION
|
HBV
and
HDV
co-infection
or
HBV
and
HCV
co-infection
have
a
worse
prognosis
than
these
infections
alone.
HDV
infection
will
only
occur
in
the
presence
of
HBV
infection
and
eradication
of
HDV
infection
is
difficult(24).
These
co-infections
are
related
to
misuse
of
infected
needles
and
lack
of
immunization
for
HBV,
a
preventable
infection,
hence,
parents
should
be
counseled
and
law
should
be
passed
that
every
child
follows
the
immunization
program
of
the
respective
country
especially
in
areas
where
HBV
and
HCV
is
endemic.
| STRATEGIES
TO
PREVENT
HEPATITIS
AND
HIV
INFECTIONS |
The
strategies
depend
upon
the
countries
in
which
the
infection
is
present
and
related
to
the
epidemiology
of
the
infection.
The
treatment
program
in
the
developing
countries
will
be
successful,
only
after
recognition
of
the
country
specific
epidemiology;
this
varies
and
is
mostly
dependent
upon
the
economic
development,
which
the
respective
country
has
achieved.
Immunization
HBV
Immunization
is
mandatory
for
the
prevention
of
HBV
infection
in
children
and
adults(25).
Despite
counseling
and
advice
to
parents
more
than
50
%
of
the
children
may
not
be
immunized
for
HBV
in
various
communities
especially
in
those
areas
which
are
economically
not
well
off(26).
Hepatitis
B
virus
infects
many
infants
and
children
-
more
than
2
billion
people
have
been
infected
with
the
virus
at
some
point,
and
an
estimated
350
million
are
lifelong
carriers.
However,
most
don't
develop
the
clinical
disease
until
several
decades
later
when
the
virus
can
cause
inflammation
of
the
liver
and
lead
to
cirrhosis
or
liver
cancer.
More
than
30
million
children
are
unimmunized
either
because
vaccines
are
unavailable,
because
health
services
are
poorly
provided
or
inaccessible,
or
because
families
are
uninformed
or
misinformed
about
when
and
why
to
bring
their
children
for
immunization.
In
such
communities
HBV
and
HCV
infections
continue
to
increase(26).
HCV
is
more
difficult
in
terms
of
prevention
of
the
disease
as
vaccine
is
not
available,
however
treatment
response
in
both
adults
and
paediatric
patients
especially
has
shown
a
good
response
with
genotype
2
and
3(27).
It
is
advisable
that
all
family
members
are
screened
for
HBV
and
HCV
if
a
case
of
HBV
or
HCV
is
detected
in
the
family(28).
In
some
hospitals
prior
to
surgery,
regular
screening
of
HBV
and
HCV
is
done
to
prevent
the
infection
in
the
surgeons,
in
case
of
a
prick
with
infected
blood
of
patient.
The
relative
importance
of
various
modes
of
transmission
of
HBV,
HCV
and
HIV
viruses
differs
in
each
country;
hence,
the
choice
of
specific
prevention
and
control
strategies
depends
primarily
on
the
epidemiology
of
infection
in
a
particular
country.
Comprehensive
hepatitis
B
prevention
strategies
should
include
(1)
prevention
of
perinatal
HBV
transmission,
(2)
hepatitis
B
vaccination
at
critical
ages
to
interrupt
transmission
and
(3)
prevention
of
nosocomial
HBV
transmission
and
(4)
counseling
of
the
parents.
The
prevention
of
hepatitis
C
is
problematic
because
a
vaccine
to
prevent
HCV
infection
is
yet
to
be
developed
in
the
foreseeable
future.
From
a
global
perspective,
the
greatest
impact
on
the
disease
burden
associated
with
HCV
infection
will
be
achieved
by
focusing
efforts
on
primary
prevention
strategies
to
reduce
or
eliminate
the
risk
for
transmission
from
nosocomial
exposures
(e.g.
blood
transfusion,
unsafe
injection
practices)
and
high-risk
practices
(e.g.
injecting
drug
use).
Studies
have
shown
that
the
risk
of
infected
blood
causing
hepatitis
and
HIV
is
still
possible
in
countries
where
appropriately
screened
blood
is
not
available.
This
is
even
more
apparent
in
thalassemic
children
requiring
repeated
blood
transfusion.
The
infected
blood
causes
increased
morbidity
and
mortality
in
the
children
due
to
thalassemia
itself
and
as
there
is
a
high
risk
of
the
children
being
co-infected
with
HBV,
HCV,
HDV
or
HIV
(29).
A
study
of
thalassemic
children
from
Karachi,
Pakistan
has
shown
that
43%
of
the
patients
were
positive
for
HCV,
5
%
for
HBV
and
none
for
HIV.
This
indicates
that
the
hepatitis
B
vaccine
is
protecting
the
children
against
HBV
and
hence
HDV.
However,
due
to
the
absence
of
vaccine
against
HCV,
there
is
a
higher
frequency
of
HCV
in
the
general
population
and
in
thalassemics
compared
to
HBV
infection.
Also,
it
is
worthwhile
to
note
that
none
of
the
patients
in
this
study
were
positive
for
HIV.
Hence,
we
have
to
be
extremely
vigilant
in
the
prevention
of
these
infections
by
creating
awareness,
education
and
counseling
of
the
parents,
children,
health
workers
and
policy
makers.
HIV
has
not
reached
the
high
proportions
seen
in
other
countries
such
as
India
and
Indonesia(14,29)
and
we
have
to
adopt
all
preventive
strategies
to
contain
HIV.
Lack
of
international
and
local
organizations
interaction
and
role
of
NGOs
NGO
can
play
a
great
role
in
the
prevention
and
treatment
of
hepatitis
and
HIV
in
the
developing
world
and
other
parts
of
the
world(30).
The
role
of
organizations
such
as
WHO,
UNICEF
and
local
organizations
in
various
countries
is
important
to
prevent
HBV,
HCV
and
HIV
in
the
paediatric
population,
due
to
the
wide
geographical
area
of
coverage
of
these
organizations,
political
will
and
available
resources.
It
has
also
been
observed
in
some
of
the
developing
countries
that
a
decrease
in
HBV
has
occurred
when
compared
to
HCV,
which
has
continued
to
rise
due
to
non-availability
of
the
vaccine
against
HCV.
International
forums
provide
treatment
of
HIV
medications
at
a
very
low
cost(10,11,23,
25).
Role
of
local
paediatricians
Pediatricians
taking
care
of
a
child
should
screen
all
children
for
HBV
and
HCV
regardless
of
the
status
of
the
parents,
especially
when
working
in
an
endemic
area.
The
child
should
be
referred
to
a
paediatric
hepatologist
for
further
investigation
and
treatment
if
found
to
be
positive
for
HBV,
HCV
alone
or
co-infected.
A
Paediatric
Infectious
disease
expert
may
be
consulted
in
the
management
of
co-infection
with
HIV.
Local
paediatricians
should
repeatedly
counsel
parents
regarding
child
abuse
especially
sexual
abuse
and
its
relation
with
HIV
or
hepatitis
to
protect
the
vulnerable
child.
The
local
infectious
disease
experts,
should
include
topics
of
HBV,
HCV
and
HIV
infection
in
children
and
their
prevention
in
international
conferences
in
developing
countries
so
to
create
awareness
among
the
Pediatricians.
Research
There
is
a
need
to
collect
data
on
the
existing
infected
paediatric
cases
of
HBV,
HCV
and
HIV
in
the
developing
countries
to
determine
the
prevalence
and
incidence
of
these
infectious
diseases.
By
doing
so
strategies
can
be
developed,
which
would
then
focus
on
the
treatment
of
the
existing
population
of
children
and
in
the
prevention
of
the
remaining
paediatric
population
existing
in
the
country.
In
a
study
conducted
in
Istanbul,
Turkey,(31)
very
early
onset
of
substance
and
polysubstance
use
indicated
easy
accessibility
of
legal
and
illicit
substances
by
children
and
youth.
These
findings
on
Turkish
children
and
youth
who
seek
substances
at
an
early
age
can
be
corrected
by
means
of
early
interventions
at
a
stage
when
the
child
has
just
started
substance
abuse.
The
diseases
such
as
HBV,
HCV
and
HIV
can
be
prevented
in
the
child
at
early
stage
by
appropriate
early
intervention
and
treatment
facility(31).
| CHALLENGES
IN
THE
DEVELOPING
COUNTRIES |
The
main
challenges
that
need
to
be
met
in
developing
countries
include
lack
of
qualitative
ongoing
training
for
health
professionals.
In
some
areas
of
the
developing
countries,
training
programs
are
non-existent,
so
that
some
health
professionals
though
aware
of
the
diseases,
do
not
have
sufficient
knowledge
for
prevention,
treatment
or
referral
to
tertiary
care
hospitals.
Inter
professional
education
(IPE)(32),
involves
close
collaboration
between
health
care
professionals
and
can
improve
patient
care.
Training
and
educational
programs
including,
continuing
medical
education
(CME),
can
be
done
so
that
the
health
professional
may
work
together
to
reach
the
objectives,
which
is
primarily
patient
care.
In
these
countries
it
is
essential
that
regular
seminars
for
health
workers
in
a
systematic
fashion
are
held
with
ethical
coverage
by
the
newsmedia
and
appropriate
discussions
with
the
public
and
health
workers
and
policy
makers
is
done,
so
that
prevention
of
HBV,
HCV
and
HIV
can
be
implemented.
Children
should
be
highlighted
at
all
levels
of
the
discussion,
including
that
of
an
expecting
mother
(unborn
baby),
her
delivery,
role
of
the
father
and
family,
so
that
control
of
the
prevention
of
HBV
and
HCV
and
HIV
can
be
done
by
immunization
and
counseling.
Policy
makers
The
role
of
policy
makers
is
crucial
for
the
prevention
of
these
infections.
Unless
the
governments
are
serious
about
the
prevention
of
these
infections,
the
disease
will
spread
and
reach
epidemic
proportions.
Hence,
even
if
few
cases
are
detected
in
any
area,
prompt
action
should
be
taken
in
terms
of
prevention
of
these
infections.
A
pertinent
example
is
China
where
there
is
a
high
prevalence
of
these
infections.
HBV
and
HCV
co-infection
in
HIV-infected
children
in
China
receiving
ART
has
prompted
policy
makers
to
routinely
screen
for
viral
hepatitis
co-infection,
organize
an
intensive
prevention
strategy
of
childhood
HBV
and
HCV
transmission,
and
develop
programs
for
the
modification
of
the
management
of
pediatric
HIV
infection(33).
Cost
effective
analysis
Analysts
are
required
to
make
cost
effective
analysis
of
the
resources(34)
available
to
decision
makers
for
the
implementation
of
the
strategies
for
the
prevention
of
hepatitis
and
HIV
especially
in
the
poor
countries.
Existing
interventions
should
be
evaluated
both
in
terms
of
outcome
as
well
as
resources,
before
a
new
intervention
is
introduced
or
approved.
Research
done
in
any
one
country
or
region
or
area
should
be
such
that
it
can
be
applied
in
another
region
with
minimum
cost.
Also
long-term
effects
need
to
be
considered;
as
an
example
lack
of
immunization
against
hepatitis
B
can
eventually
lead
to
HCC
especially
if
the
patient
is
exposed
to
the
risk
factors
leading
to
HBV
infection.
In
such
a
case
the
cost
effective
analysis
of
the
intervention
i.e.
the
immunization
for
HBV
is
definitely
a
good
preventive
strategy
as
HCC
can
be
prevented.
In
the
long
run
cost
of
immunization
is
negligible
compared
to
the
treatment
for
HCC
and
let
alone
the
morbidity
associated
with
HCC.
Hence,
an
economic
analysis
should
always
be
done
keeping
in
mind
the
objectives
of
the
strategies,
which
will
be
used
to
prevent
infective
diseases
such
as
HBV,
HCV
and
HIV
in
the
very
vulnerable
human
population,
our
children
in
regions
of
the
world,
which
are
impoverished(34).
In
this
regard
it
is
essential
to
develop
vaccines
for
HCV(35)
and
HIV,
which
can
prevent
these
infections
and
will
be
cost
effective
in
the
long
run.
A
young
19
year
old
woman
of
Afghani
origin
is
married
to
a
Pakistani
man,
as
her
family
is
very
poor
and
need
the
money,
which
will
be
obtained
from
this
marriage
and
as
is
the
custom
that
money
is
given
to
the
father
of
the
bride.
This
is
the
Pakistani
man's
second
marriage.
They
are
living
in
an
area
which
is
a
slum
area/camp,
where
there
are
migrating
individuals
from
various
parts
of
country
Pakistan
and
people
who
have
fled
from
Afghanistan
due
to
the
war.
Within
a
year
a
beautiful
healthy
baby
boy,
green
eyes
and
golden
hair,
resembling
his
parents
and
grandparents
is
born.
Living
in
an
area
of
suburb
of
a
major
city
of
Pakistan,
delivery
takes
place
at
home.
Parents
due
to
lack
of
awareness
do
not
immunize
the
baby.
Mother
breastfeeds
for
9
months
exclusively.
Weaning
is
inappropriate
and
the
child
gradually
becomes
malnourished
and
plots
on
the
3rd
centile
for
both
height
and
weight.
Gradually
he
becomes
stunted
by
the
age
of
5
years.
Mother
is
unable
to
give
him
attention
and
food
due
to
poverty,
lack
of
awareness
and
education
and
little
economic
support
from
the
husband
or
the
family.
The
mother
herself
has
lost
weight
and
now
looks
like
a
middle-aged
woman,
even
though
she
is
only
26
years
of
age.
She
now
has
2
more
children
ages
4
and
2,
with
the
same
nutrition
history.
These
children
play
in
rubbish,
(Figure
1)
as
their
only
means
of
recreation
in
the
area.
A
nearby
man
has
developed
tuberculosis
and
is
seen
coughing
out
blood,
by
some
of
the
neighbors.
Another
individual
aged
23
years;
living
nearby
due
to
severe
depression
has
started
taking
drugs
of
all
sorts.
Later
he
is
diagnosed
to
have
HIV.
Infected
needles
are
thrown
by
this
man
and
his
community
in
the
same
rubbish
where
young
children
play(36).
Figure
1:
Child
playing
in
garbage
with
infected
needles,
in
a
poor
community
area,
with
no
supervision,
lack
of
awareness
and
lack
of
education
Despite
the
local
government
emphasizing
immunization,
very
few
children
in
the
community
are
vaccinated,
due
to
their
own
myths.
This
community
is
close
knit
and
do
not
always
welcome
NGOs
or
local
doctors.
They
do
not
allow
their
children
to
go
to
regular
schools
and
the
boys
as
soon
as
possible
go
out
to
work,
which
can
be
anywhere
between
8
and
12
years
of
age.
The
young
boy
aged
5
years
now
goes
on
a
donkey
cart
all
over
the
city
with
his
older
cousin,
picking
up
old
used
stuff
including
used
needles
and
supplying
them
to
a
local
factory
where
they
are
recycled
and
used
again
in
all
major
hospitals.
He
has
by
now
become
infected
with
HBV
and
HCV.
He
is
also
immune-compromised.
Due
to
frequent
visits
to
a
distant
relative
with
Tuberculosis;
the
child
is
now
also
exposed
to
TB.
The
child
is
now
6
years
of
age,
and
looks
like
a
wizened
old
person
with
no
concept
of
childhood
play
and
is
brought
to
clinic
finally
as
he
is
listless,
severely
malnourished
with
low
grade
fever
every
night.
On
further
investigation
he
is
found
to
be
HBV,
HCV
and
HIV
positive.
There
is
sharing
of
toothbrush,
comb
etc.
by
all
the
children
due
to
non-affordability
and
lack
of
knowledge
and
awareness
in
the
family.
His
sister
who
also
develops
HCV
is
given
treatment
by
the
NGO
and
in
part
by
government
funds
from
a
local
hospital.
The
girl
becomes
HCV
negative,
but
the
boy
despite
available
treatment
dies.
This
scenario
exists
in
many
parts
of
both
these
neighboring
countries
and
is
increasing
in
frequency.
This
family
like
many
others
will
be
prone
to
the
following
causes
of
hepatitis
and
HIV
co-infection.
The
prevention
strategies
for
such
children
are
described
in
the
table
below.
Table
1:
Strategies
for
the
Prevention
of
HBV
(hepatitis
B),
HCV
(hepatitis
C)
and
HIV
in
the
Paediatric
Population
of
Developing
Countries
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